title: Self-organization of muscle cell structure and function.
abstract: The organization of muscle is the product of functional adaptation over several length scales spanning from the sarcomere to the muscle bundle. One possible strategy for solving this multiscale coupling problem is to physically constrain the muscle cells in microenvironments that potentiate the organization of their intracellular space. We hypothesized that boundary conditions in the extracellular space potentiate the organization of cytoskeletal scaffolds for directed sarcomeregenesis. We developed a quantitative model of how the cytoskeleton of neonatal rat ventricular myocytes organizes with respect to geometric cues in the extracellular matrix. Numerical results and in vitro assays to control myocyte shape indicated that distinct cytoskeletal architectures arise from two temporally-ordered, organizational processes: the interaction between actin fibers, premyofibrils and focal adhesions, as well as cooperative alignment and parallel bundling of nascent myofibrils. Our results suggest that a hierarchy of mechanisms regulate the self-organization of the contractile cytoskeleton and that a positive feedback loop is responsible for initiating the break in symmetry, potentiated by extracellular boundary conditions, is required to polarize the contractile cytoskeleton.
authors.affiliation: Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Grosberg
authors.forename: Po-Ling
authors.initials: PL
authors.lastname: Kuo
authors.forename: Chin-Lin
authors.initials: CL
authors.lastname: Guo
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Geisse
authors.forename: Mark-Anthony
authors.initials: MA
authors.lastname: Bray
authors.forename: William J
authors.initials: WJ
authors.lastname: Adams
authors.forename: Sean P
authors.initials: SP
authors.lastname: Sheehy
authors.forename: Kevin Kit
authors.initials: KK
authors.lastname: Parker
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology; D022001:Focal Adhesions / Q000737:chemistry / Q000502:physiology; D007150:Immunohistochemistry; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009210:Myofibrils / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000378:metabolism / Q000502:physiology
chemical_list: D000199:Actins